The role of PML in the control of apoptotic cell fate: a new key player at ER–mitochondria sites

The role of PML in the control of apoptotic cell fate: a new key player at ER–mitochondria sites

P Pinton, C Giorgi, and PP Pandolfi

The development of malignant tumors results from deregulated proliferation or an inability of cells to undergo apoptotic cell death. Experimental works of the past decade have highlighted the importance of calcium (Ca2þ) in the regulation of apoptosis. Several studies indicate that the Ca2þ content of the endoplasmic reticulum (ER) determines the cell’s sensitivity to apoptotic stress and perturbation of ER Ca2þ homeostasis appears to be a key component in the development of several pathological situations. Sensitivity to apoptosis depends on the ability of cells to transfer Ca2þ from the ER to the mitochondria. The physical platform for the interplay between the ER and mitochondria is a domain of the ER called the mitochondria-associated membranes (MAMs). The disruption of these contact sites has profound consequences for cellular function, such as imbalances of intracellular Ca2þ signaling, cellular stress, and disrupted apoptosis progression. The promyelocytic leukemia (PML) protein has been previously recognized as a critical and essential regulator of multiple apoptotic response. Nevertheless, how PML would exert such broad and fundamental role in apoptosis remained for long time a mystery. In this review, we will discuss how recent results demonstrate that the elusive mechanism whereby the PML tumor suppressor exerts its essential role in apoptosis triggered by Ca2þ-dependent stimuli can be attributed to its unexpected and fundamental role at MAMs in the control of the functional cross-talk between ER and mitochondria.

Author pronuvia

Pronuvia is dedicated to improving the lives of patients with ongoing clinical trials and research. We are also focused on lowering health care costs by developing simple but innovative and effective treatments. Bringing optimum health to general public affordably and painlessly is the grand ambition of Pronuvia. Our research continues.

This website is intended to inform and educate medical professionals. It is not intended for patients. It also does not seek to make claims about the effectiveness of SAC calcium in medical treatment.

Regulated calcium intake can have manifold health effects. Too much or too little calcium and even wrong types of calcium can affect our health negatively. Only ionic calcium plays important physiological functions in our body, and yet many people have chronic ionic calcium deficiency. This site serves to inform medical professionals about ionic calcium’s potential in treating calcium-related diseases by introducing numerous third-party researches done. However, ionic calcium treatment is still an evolving field, and clinical studies are still insufficient to determine its effectiveness.

SAC calcium’s higher solubility provides needed amount of ionic calcium to trigger calcium homeostasis. While Pronuvia’s SAC calcium has Canadian FDA registration (NPN 80043292) and is produced in a FDA compliant laboratory, it has not been approved as a therapeutic treatment.

Patients interested in SAC calcium therapy are advised to consult a participating physician to participate in a clinical trial.